Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.

Safety and efficacy of intranasal insulin in patients with Alzheimer's disease: a systematic review and meta-analysis.

Background and Aim: We performed this meta-analysis to evaluate the safety and efficacy of intranasal insulin in Alzheimer's disease (AD) patients. Methods: A literature search was conducted for PubMed, Scopus, and Web of Science from inception until August 2022. Documents were screened for qualified articles, and all concerned outcomes were pooled as risk ratios or mean difference (MD) in the meta-analysis models using Review Manager (RevMan version 5.4). Results: Our results from 12 studies favored intranasal insulin over placebo in terms of Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-cog) 20 IU, (MD = -0.13, 95% CI [-0.22, -0.05], P = 0.003). The overall effect did not favor either of the two groups for ADAS-cog 40 IU, memory composite 20 IU and 40 IU, and adverse events (MD = -0.08, 95% CI [-0.16, 0.01], P = 0.08), (MD = 0.65, 95% CI [-0.08, 1.39], P = 0.08), (MD = 0.25, 95% CI [-0.09, 0.6], P = 0.15), and (MD = 1.28, 95% CI [0.75, 2.21], P = 0.36), respectively. Conclusion: Ultimately, this meta-analysis showed that intranasal insulin in small doses (20 IU) significantly affects patients with AD. Further studies are recommended on reliable insulin delivery devices to increase insulin in the central nervous system. Relevance for Patients: Intranasal insulin has shown promising results in treating patients with AD. The lower doses (20 IU) can play a positive role in improving the disease. As research continues, it is likely that this treatment will become more widely accepted and utilized in clinical practice.